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dc.contributor.authorBravo, Francisca Vazpor
dc.contributor.authorDa Silva, Jorgepor
dc.contributor.authorChan, Robin Barrypor
dc.contributor.authorDi Paolo, Gilbertpor
dc.contributor.authorTeixeira-Castro, Andreiapor
dc.contributor.authorOliveira, Tiago Gilpor
dc.description.abstractPhospholipase D (PLD) is a key player in the modulation of multiple aspects of cell physiology and has been proposed as a therapeutic target for Alzheimer's disease (AD). Here, we characterize a PLD mutant, pld-1, using the Caenorhabditis elegans animal model. We show that pld-1 animals present decreased phosphatidic acid levels, that PLD is the only source of total PLD activity and that pld-1 animals are more sensitive to the acute effects of ethanol. We further show that PLD is not essential for survival or for the normal performance in a battery of behavioral tests. Interestingly, pld-1 animals present both increased size and lipid stores levels. While ablation of PLD has no important effect in worm behavior, its ablation in an AD-like model that overexpresses amyloid-beta (Aβ), markedly improves various phenotypes such as motor tasks, prevents susceptibility to a proconvulsivant drug, has a protective effect upon serotonin treatment and reverts the biometric changes in the Aβ animals, leading to the normalization of the worm body size. Overall, this work proposes the C. elegans model as a relevant tool to study the functions of PLD and further supports the notion that PLD has a significant role in neurodegeneration.por
dc.description.sponsorshipWe would like to thank members of the Oliveira and Maciel labs for discussions, for critical analysis of data and discussions on the manuscript. Ricardo Rosa for his technical assistance in lifespan assays and Carlos Bessa for his technical suggestions. Thanks to the Caenorhabditis Genetics Center (CGC), which is funded by the National Institutes of Health – National Center for Research Resources, for some of the nematode strains. Costs with acquisition and transfer of genetic C. elegans models were covered by Tiago Gil Oliveira. This work was supported by grants from the Portuguese North Regional Operational Program (ON.2 – O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER), the Portuguese Foundation for Science and Technology PD/BD/52286/2013 (Francisca Vaz Bravo) as well as NIH ADRC grant P50 AG008702 to Scott A. Small (project G.D.P.) and NIH grant R21 AG045020 to G.D.P.por
dc.publisherNature Publishing Grouppor
dc.titlePhospholipase D functional ablation has a protective effect in an Alzheimer's disease Caenorhabditis elegans modelpor
dc.subject.wosScience & Technologypor
sdum.journalScientific Reportspor
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